TheconceptofurineaniongapduringametabolicacidosisassumesthatthemajorcationsinurineareNa+ ,K+ ,andNH4+ andthatthemajoranionisCl− (withurinepH< 6.5,virtuallynoHCO3− ispresent).AsaresulttheurineaniongapwillyieldanegativevaluewhenNH4+ isbeingexcreted.Indeed,theabsenceofaurineaniongaportheexistenceofapositivevalueindicatesarenaldefectinNH4+ productionandexcretion.
gBoth RhBG and RhCG transport NH3. There is some evidence that RhBG may also transport some NH4 + .
•Fig. 37.7 Production,transport,andexcretionofNH4+bythenephron.GlutamineismetabolizedtoNH4+andHCO3−intheproximaltubule.TheNH4+issecretedintothelumen,andtheHCO3−enterstheblood.ThesecretedNH4+isreabsorbedinHenle’sloop,primarilybythethickascendinglimb,andaccumulatesinthemedullaryinterstitium.NH3issecretedbythecollectingductviarhesusglycoproteins,andH+secretiontrapsNH4+inthelumen.ForeachmoleculeofNH4+excretedintheurine,amoleculeof“new”HCO3−isaddedbacktotheECF.CA,carbonicanhydrase.Tubular fluid Tubular fluid CO2 + H2O NH4 + NH4 + 2NH4 + NH4 + NH3 NH3 NH4 + NH4 + NH3 + H+ NH4 + NH4 + NH4 + NH4 + H˜NH3HCO3 – Blood Blood Na+ Na+ H+H+ Glutamine A= 2HCO3 – CA
In the net, one new HCO3 − is returned to the systemic circulation for each NH4 + excreted in the urine.
An important feature of the renal NH4 + system is that it is regulated by systemic acid-base balance. As already described, cortisol levels increase with acidosis, as does angiotensin II secretion into the lumen of the proximal tubule. Both cortisol and angiotensin II stimulate ammoniagenesis (i.e., NH4 + production from glutamine). During systemic acidosis, the enzymes in the proximal tubule cell responsible for metabolism of glutamine are stimulated. This involves synthesis of new enzyme and requires several days for complete adaptation. With increased levels of these enzymes, NH4 + production is increased, allowing enhanced production of new HCO3 − . Conversely, glutamine metabolism is reduced with alkalosis. Acidosis also increases the abundance of RhBG and RhCG in the collecting duct. Thus the ability to secrete NH4 + is also enhanced.
Response to Acid-Base Disorders
The pH of the ECF is maintained within a very narrow range (7.35–7.45).
Inspection of
Eq. 37.3 shows that the pH of hFor simplicity of presentation in this chapter, the value of 7.40 for body fluid pH is used as normal, even though the normal range is from 7.35 to 7.45. Similarly the normal range for PCO2 is 35 to 45 mm Hg. However, a PCO2 of 40 mm Hg is used as the normal value. Finally, a value of 24 mEq/L is considered a normal ECF [HCO3 −], even though the normal range is 22 to 28 mEq/L.